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HMGB1 as a new biomarker of celiac disease in children: A multicenter study
Sara Manti1, Caterina Cuppari1, Lucia Tardino2
1Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy.
Insights
Serum high mobility group box 1 (HMGB1) levels are elevated in children diagnosed with celiac disease (CD), particularly in typical forms, correlating with disease severity.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Molecular Biology
Background:
- Celiac disease (CD) diagnosis can be delayed due to varied symptoms and diagnostic challenges.
- High mobility group box 1 (HMGB1) is implicated in inflammation and gastrointestinal barrier dysfunction.
Purpose of the Study:
- To measure serum HMGB1 levels in children with CD at diagnosis.
- To investigate the association between serum HMGB1 levels and clinical/histological CD phenotypes.
Main Methods:
- Assessed serum HMGB1 levels, celiac-specific antibodies, and duodenal histology in 49 children with CD and 44 controls.
- Classified CD phenotypes as typical, atypical, or silent.
- Utilized Marsh classification for mucosal lesions.
Main Results:
- Serum HMGB1 levels were significantly higher in children with CD compared to healthy controls.
- HMGB1 levels differed significantly across typical, atypical, and silent CD forms.
- HMGB1 levels correlated with Marsh classification grades, indicating higher levels with more severe villous atrophy.
Conclusions:
- High mobility group box 1 (HMGB1) is upregulated in children with celiac disease at diagnosis.
- Elevated HMGB1 levels are particularly pronounced in the typical CD form.
- Serum HMGB1 levels reflect the histological severity of celiac disease.
Objective:
Despite the availability of specific sierology and point-of-care tests, the phenotypic heterogeneity and the symptoms fluctuation as well as the "open-window" existing among the late and silent forms cause often a delayed celiac disease (CD) diagnosis. Recently, it has been reported that high mobility group box 1 (HMGB1) mediates inflammation and gastrointestinal barrier failure. The aim of this study was to detect serum HMGB1 levels at CD diagnosis and to evaluate the relationship between serum HMGB1 levels and clinical and histologic phenotypes.
Methods:
49 CD children and 44 healthy children were enrolled. Specific antitissue transglutaminase type 2, antideaminated form of gliadin antibodies, serum HMGB1 levels, and typical histopathological changes in duodenal mucosa were performed in all patients. Mucosal lesions were classified according to Marsh classification. In relation to clinical presentation, we classified patients into: typical, atypical and silent forms.
Results:
Serum HMGB1 levels were significantly higher in those with CD than those in the healthy control group (P < 0.001). Significant differences in serum HMGB1 levels were detected in children with typical CD form compared to both children with atypical CD form (P < 0.001) and children with silent CD form (P < 0.001). By using the Marsh classification, significant differences were found between subjects with grade 3 B-B1 and 3 C-B2 and villous atrophy, respectively (P < 0.05). On the contrary, no significant differences in serum HMGB1 levels in subgroups of children with grade 3 A compared to grade 3 B-B1 were detected.
Conclusions:
HMGB1 is upregulated at diagnosis in all CD children, especially in typical form, and reflecting the histologic severity of disease.